Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.21.37 (neutrophil elastase)
 4,078 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of human neutrophil elastase (HNE), cathepsin-G, H2O2, xanthine oxidase-hypoxanthine derived superoxide anion and endotoxin on the PGI2 production by cultured bovine pulmonary endothelial cells were observed. The results showed that HNE, superoxide anion and H2O2 could decrease the PGI2 production by endothelial cells, and cathepsin-G had no effect on the production of PGI2. In our experiment, endotoxin could enhance PGI2 production. It was suggested that HNE, superoxide anion, and H2O2 may be involved in the pathogenesis of pulmonary hypertension.
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PMID:[Effect of human neutrophil elastase, cathepsin--G. superoxide anion and endotoxin on the PGI2 production by cultured bovine pulmonary endothelial cells]. 180 32

The addition of either cathepsin-G or leukocyte elastase to endotoxin-stimulated human peripheral blood monocytes decreased the immunoreactive tumor necrosis factor (TNF) detected in culture supernatants in a concentration-dependent manner. Both enzymes also induced a loss of supernatant cytolytic activity as determined on the WEHI-164 target cell line. Incubation of recombinant human TNF and lymphotoxin (LT) with either cathepsin-G or leukocyte elastase resulted in a loss of cytokine bioactivity. Examination of enzyme-treated recombinant cytokines by gel electrophoresis revealed that cathepsin-G cleaved LT into a 12.6-kDa fragment and leukocyte elastase fragmented LT into a 14.1-kDa product. On Western blots cathepsin-G and leukocyte elastase degraded TNF into 11- and 7.6-kDa fragments, respectively. Incubating leukocyte elastase with plasma elastase inhibitor alpha-1-antitrypsin prevented the loss of recombinant TNF bioactivity and blocked the degradation of this cytokine. This study suggests that two of the most abundant neutrophil proteases, cathepsin-G and leukocyte elastase, may be important regulators of TNF and LT bioactivity.
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PMID:Cathepsin-G and leukocyte elastase inactivate human tumor necrosis factor and lymphotoxin. 203 73

The endothelial cells of pulmonary blood vessel play an significant role in lung vessel permeability, especially in acute lung damage and adult respiratory distress syndrome. In this study, bovine pulmonary endothelial cells were isolated, cultured and identified by means of reverse microscopic, scanning electromicroscopic, transmission electro- microscopic and immunofluorescence microscopic observation. Then they were labeled with 51Cr. Hydrogen peroxide (H2O2), H2O2 with catalase, xanthine oxidase (XO) with hypoxanthine (HX), human neutrophil elastase (HNE), cathepsin-G (C-G) and endotoxin (ET) were incubated with the labeled cells for half hour in various experimental groups respectively. The amount of 51Cr in the suspension released from the damaged cells was counted with r-radiometer. The results show that HNE, ET, H2O2 and superoxide anion (the latter is produced from the reaction between XO and HX) could at some degree damage the membrane of endothelial cells, and the inflammatory mediators of human neutrophils might play an important role in the development of pulmonary edema.
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PMID:[Effect of the products released from the activated human neutrophils and endotoxin on bovine pulmonary endothelial cells]. 208 56

We investigated the mechanism of cartilage degradation by pancreatic elastase as a model system for the action of cationic proteases such as leukocyte elastase and cathepsin-G. It is shown that the cationic properties of elastase contribute to its proteolytic potential with respect to cartilage degradation. Elastase preparations with neutral or negative charge, obtained by chemical modification were far less effective in cartilage degradation than the cationic, native enzyme. Modification of elastase did not affect the active site of the enzyme as shown by kinetic studies, nor did it alter the complexing with alpha-1-proteinase inhibitor. Quantitative and autoradiographic studies indicate that the positive charge of the enzyme favors the penetration in cartilage and interaction with the polyanionic proteoglycan substrate. It is concluded that the potent cartilage-degrading activity of elastase is dependent on charge-mediated interactions with its substrate.
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PMID:Degradation of cartilage proteoglycans by elastase is dependent on charge-mediated interactions. 336 81

Eglin-c is a naturally occurring polypeptide of 70 amino acids with a molecular mass of 8,100 daltons. It is a strong inhibitor of human neutrophil elastase (HNE) and cathepsin-G, and, when given intratracheally to hamsters 1 h before human neutrophil elastase, it can prevent or ameliorate the emphysema produced by HNE. The present experiments were designed to determine the duration of the effectiveness of eglin-c, prepared by DNA technology from Escherichia coli, in preventing the emphysema and secretory cell metaplasia induced by HNE. Eglin-c (2,000 micrograms in 0.5 ml saline) was effective in ameliorating emphysema, as determined histologically and physiologically, when it was given intratracheally to hamsters 1, 2, 4, and 8 h before the intratracheal instillation of 300 micrograms of HNE. Eglin-c ameliorated bronchial secretory cell metaplasia when given 1 h before HNE but not when the time intervals were 2 h or longer. The clearance of [3H]eglin-c from the lungs was assessed. Four h after intratracheal instillation of 446 micrograms of [3H]eglin-c, 33% of the tritium was found in the lung tissue and bronchoalveolar lavage fluid; 83% of the radioactivity in the lavage fluid supernatant was associated with functionally active eglin-c. No evidence of bronchopulmonary toxicity was seen in hamsters given 4 intratracheal instillations of 2,000 micrograms of eglin-c at 1-wk intervals.
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PMID:Effect of varying the time interval between intratracheal administration of eglin-c and human neutrophil elastase on prevention of emphysema and secretory cell metaplasia in hamsters. With observations on the fate of eglin-c and the effect of repeated instillations. 353 70

Cleavage of C3 by purified leukocyte enzymes and crude extracts of human polymorphonuclear leukocyte (PMN) granules has been reported. We demonstrate that viable PMN mediate the cleavage of erythrocyte-bound C3b and C3bi via cell-associated proteases. Greater than 50% of 125IC3(x) was released from EAC43bix during a 5-min incubation with viable PMN at 37 degrees C. More than a 30-min incubation was required for substantial release from EAC43bx. Culture fluids from PMN suspensions had limited cleaving ability; cleavage of cell-bound C3bx and C3bix was only partially reduced when PMN were preincubated with high levels of soluble C3 which completely blocked EAC43b rosettes. Thus, cell-to-cell contact between opsonized erythrocytes and viable PMN with surface-associated proteases are responsible for cleavage of these opsonic sites. The effect of defined protease inhibitors on PMN cleaving activity as well as on purified leukocyte elastase was examined. Phenylmethylsulfonyl fluoride (PMSF) and the leukocyte elastase inhibitor, methoxy-succinate-alanine-alanine-valine-chloromethyl ketone (MeO) each inhibited cleavage of C3b by 90% and C3bi by 60%. In contrast, the cathepsin-G inhibitor, benzyloxy-carbonyl-glycine-leucine-phenylalanine-chloromethyl ketone (Z) inhibited C3b and C3bi cleavage by less than 20 and less than 5%, respectively. Ethylenediaminetetra-acetate (EDTA), which had a minimal effect on soluble leukocyte elastase, also inhibited PMN-related release. Thus, elastase appeared to be the principle but not the only enzyme responsible for cleavage of C3b and C3bi. PMSF and MeO had a minimal effect on the activity of purified C3bINA (Factor I); and PMN-mediated release of C3b fragments was not inhibited by anti-Factor I and anti-beta 1H (Factor H) IgG and Fab. Thus, these control proteins are not involved in the PMN-mediated cleavage under study. PMN-mediated cleavage of C3b was also inhibited when PMSF- and MeO-treated PMN were washed to remove the fluid phase phase protease inhibitor before adding EAC43b. This suggests that proteases localized in the PMN membrane, prior to the adherence of EAC43b, are responsible for C3b cleavage. Normal human serum was effective in blocking PMN-mediated release activity, while serum from alpha 1 antitrypsin-deficient patients was minimally effective. This suggests a mechanism for the in vivo regulation of PMN-mediated release of C3b and C3bi from opsonized particles by the natural plasma protease inhibitors.
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PMID:Cleavage of membrane-bound C3b and C3bi by viable human neutrophils (PMN). 660 72

Human leukocyte cathespin G strongly stimulates the rate of solubilization of human lung elastin by human leukocyte elastase. For instance, the elastolytic activity of an equimolar mixture of elastase and cathepsin G is more than 5 times higher than that of elastase alone. Optimal stimulation occurs only if cathepsin G and elastase act simultaneously on elastin. Potentiation of leukocyte elastase digestion of lung elastin may also be brought about by bovine alpha-chymotrypsin. This enzyme is about half as efficient as cathepsin G. Stimulation of leukocyte elastase activity by cathepsin G is about 3 times less pronounced with bovine ligamentum nuchae elastin than with human lung elastin. On the other hand, the elastolytic activity of porcine pancreatic elastase is only enhanced by 20 to 30% by cathepsin. Therefore, maximal potentiation of elastolysis occurs with the lung elastin/leukocyte elastase system. The pathologic relevance of these findings is discussed.
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PMID:Stimulation of the elastolytic activity of leukocyte elastase by leukocyte cathepsin G. 691 62

alpha 1-Antitrypsin (alpha 1-AT) is one of the major proteinase inhibitors in serum. Its primary physiological function is to inhibit neutrophil elastase activity in lung, but it also inhibits other serine proteases including trypsin, chymotrypsin, thrombin, and cathepsin. We have previously reported a novel alpha 1-AT, S-2 isoform, from rabbit that is induced up to 100-fold in the liver during acute inflammatory condition (Ray, B. K., Gao, X., and Ray, A. (1994) J. Biol. Chem. 269, 22080-22086). Here, we present evidence that the expression of this alpha 1-AT S-2 gene is also induced in lipopolysaccharide (LPS)-treated peripheral blood monocytes. From the cloned genomic DNA, we have identified a distal LPS-responsive enhancer located between -2438 and -1990 base pairs upstream of the transcription start site. In vitro DNA-binding studies demonstrated an interaction of an LPS-inducible NF-kappa B-like nuclear factor with a kappa B-element present in this enhancer region. Antibodies against p65 and p50 subunits of NF-kappa B supershifted the DNA-protein complex. A mutation of the NF-kappa B-binding element virtually abolished the LPS-responsive induction of the chimeric promoter in monocytic cells. Furthermore, overexpression of NF-kappa B induced the wild-type promoter activity. Taken together, these results demonstrated that during LPS-mediated inflammation, NF-kappa B/Rel family of transcription factors play a crucial role in the transcriptional induction of the inflammation responsive alpha 1-AT gene.
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PMID:Role of a distal enhancer containing a functional NF-kappa B-binding site in lipopolysaccharide-induced expression of a novel alpha 1-antitrypsin gene. 749 48

CD43 (sialophorin, leukosialin), an O-glycosylated and sialylated membrane protein (surface sialomucin) with antiadhesive properties, is thought to protect circulating leukocytes by preventing cell surface interactions. Although it is resistant to several proteases, the granule enzyme elastase was recently implicated in loss of extracellular CD43 regions from incubated neutrophils. Flow cytometry showed that neutrophil CD43 is cleaved by low levels of neutrophil elastase with half-maximal cleavage at 5 micrograms/mL; pancreatic elastase, in contrast, did not cleave CD43. Related neutrophil granule proteases proteinase-3 and cathepsin-G did not cleave CD43 or required greater than 10-fold higher enzyme levels, respectively. The 115-kD CD43 isoform on T-lymphoid cells, which differs in glycosylation from 135-kD neutrophil CD43, was equally sensitive to neutrophil elastase, suggesting that cleavage susceptibility extends to various leukocytes. Enzymatic removal of sialic acid did not facilitate CD43 cleavage by neutrophil elastase, a feature that distinguishes the action of neutrophil elastase from other proteases. Western blots of elastase-treated neutrophils detected an 83-kD CD43 fragment that, together with the released 52-kD fragment and 40-kD subfragment, accounts for the entire molecule and indicates that CD43 is cleaved at two sites only, releasing the distal approximately 40% of the sialomucin region. The specificity of the CD43 cleaving reaction was shown by the insensitivity of other neutrophil and lymphoid surface proteins to elastase levels that deplete CD43. Exceptions were P-selectin glycoprotein ligand-1 on neutrophils, also a surface mucin, and CD16 (Fc gamma RIII), which was previously characterized as elastase sensitive. The sensitivity and specificity of CD43 cleavage by neutrophil elastase, the very high levels of elastase in human neutrophils and its ready release by stimulating conditions suggest important physiologic/pathologic roles for this CD43 cleaving reaction.
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PMID:Specific sensitivity of CD43 to neutrophil elastase. 856 49

Human lung macrophages express all four of the known lysosomal thiol proteases: cathepsins B, H, L, and S. These enzymes share a similar size and targeting mechanism for lysosomal accumulation and all have relatively indiscriminate substrate specificity in comparison with such highly selective serine proteases as urokinase or thrombin. These enzymes do have distinctive properties: only cathepsin B has C-terminal dipeptidase activity, only cathepsin H has potent aminopeptidase activity, and only cathepsin L and S are elastolytic. Cathepsin S is unique in that it is stable at neutral pH; indeed, at neutral pH it has elastolytic activity roughly comparable with that of neutrophil elastase. Recent studies of the differential expression of these cathepsins suggest they not only cooperate in terminal degradation of endocytized protein but also have specific functions such as proenzyme activation, antigen processing, and tissue remodeling, especially bone matrix resorption. Lysates of lung macrophages degrade elastin at neutral pH, suggesting that necrosis of macrophages at sites of macrophage accumulation, e.g., caseation necrosis, could contribute to tissue destruction. Tissue destruction and remodeling by thiol proteases expressed by live macrophages, however, is limited by tight compartmentalization of cathepsins to lysosomes. Nonetheless, macrophages accumulate at sites of known injury in cigarette smokers. Because these cells contain potent elastases, and because lysosomal enzyme release and cell surface acidification are regulated events, dysregulation of thiol protease expression in stimulated macrophages may contribute to the injury observed in cigarette smokers with non-alpha-1-protease inhibitor-type emphysema.
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PMID:The role of thiol proteases in tissue injury and remodeling. 795 52


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